Abstract
The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal–Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.
Highlights
The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide
The current study is reporting the SPINK7 expression changes among the OSCC stages and we propose this protein as a "new biomarker” associated with the natural progression of the OSCC
We found differences among the oral epithelial organization in dysplasia and less or highly invasive OSCC groups, and these results were correlated with the literature[48,49], showing a differential gene expression profile by qPCR analysis with a distinctive "molecular signature” in each stage
Summary
The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Serine Peptidase Inhibitor, Kazal Type 7 (SPINK7, ECRG2) belongs to a family of 13 members (1–13) of proteins with inhibitory Serine Peptidase activity identified in 1998 in esophageal tissue[11] This novel tumor suppressor gene was identified as such by comparing normal esophageal epithelia and primary squamous cell carcinoma tissues[12,13]. HER2 ( known as C-erbB-2/ ERBB2/ErbB2) plays a critical role in cell proliferation, survival, migration, angiogenesis, and metastasis through a variety of intracellular signaling cascades such as MAPK/ERK1/2 and Pi3K/Akt[18,19] An imbalance in these pathways can lead to permanent activation[20,21]. The SPINK6 protein is secreted and acts as a functional regulator of nasopharyngeal carcinoma cell metastasis through the binding to the EGFR extracellular d omain[23]
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